Field of the Disclosure
The present disclosure relates to a scaffold for hard tissue regeneration comprising an active ingredient for treating osteoporosis and a preparation method thereof.
Description of the Related Art
The average life expectancy has significantly increased due to the rapid economic development and the advancement of medical technology. As a result, the aged population has increased and accordingly the prevalence rate of various degenerative bone diseases including osteoporosis has been increased as well. Osteoporosis is a cause of various bone defects including fracture. To treat osteoporosis, bone graft materials such as bone filler, bone binder, implant, and porous scaffold are needed. Osteoporosis patients demonstrate poorer bone density, bone volume, and bone quality. Thus, when a bone graft material including a general porous scaffold is transplanted, secondary bone damage might be induced owing to the differences of the physical properties. So, a material customized for osteoporosis patients has to be developed. A scaffold can be used in order to induce regeneration of tissue via a self recovering system. The scaffold acts as a bridge connecting the tissues, and thus it has to be designed to be decomposed at the same speed as the bone regeneration. That is, if the bone regeneration occurs faster than the decomposition of the scaffold, the scaffold can hinder the bone regeneration, and if the bone regeneration is slower than the decomposition of the scaffold, that means the scaffold is decomposed before the bone regeneration, the full effect of the scaffold cannot be expected.
In general, the osteoblast activity to make bone is weaker than the osteoclast activity to absorb bone in an osteoporosis patient. Therefore, a porous scaffold developed for normal people does not fit for osteoporosis patients. To bring full effect of the scaffold, it is necessary to increase the osteoblast activity and at the same time to inhibit the osteoclast activity in the transplantation area.
The osteoporosis treating agents used clinically today are largely divided into two groups, which are bone resorption inhibitors and bone forming agents. The bone resorption inhibitor is exemplified by bisphosphonate, female hormone (estrogen), female hormone receptor modulator, and calcitonin. Among these, the bisphosphonate-based drug is most frequently prescribed as the primary drug for treating osteoporosis. However, this drug is apt to be accumulated in the inside of body, so that serious side effects including mandible necrosis can be induced if it is administered for a long term or at a big dose. It has been considered to use a growth factor like BMP (bone morphogenic proteins) that is excellent in inducing bone tissue generation as a bone forming agent, but it is mostly produced in foreign countries by taking advantage of genetic recombination technique and thus it is sold expensive here. That means, medical costs to apply the drug to bone defect caused by osteoporosis is a burden. In the meantime, various food components have been studied not as a treating agent but as a preventive agent or as nutrients efficient for osteoporosis, and they have been orally-administered to prevent osteoporosis. Studies are undergoing in order to increase the efficiency by adding gel or patty type bone filler with the above osteoporosis treating materials (patent reference 1) and by adding such metal ions (zinc, copper, iron, magnesium, silver, and strontium) that bring favorable effect on bone formation to a bone graft material to be released later on.
In particular, the scaffold based on ceramic which is similar in properties to the mineral component of human bone has to be prepared by high temperature sintering considering the characteristics of ceramic process. So, if a drug or a growth factor, which is vulnerable to heat, is used, it has to be added after the high temperature sintering. The method for adding such a material is that a drug or a growth factor dispersed in a solution is adsorbed on the surface of a scaffold. However, this procedure causes early quick release of the drug and makes the long time sustained-release difficult. Besides, the amount of the drug added therein is limited also. Therefore, the method using ceramic mixed with natural or synthetic polymer or added with such metal ions not vulnerable to heat treatment is more general these days. However, the former has a disadvantage of difficulty in expecting good mechanical properties and bioactivity and the latter has a disadvantage of difficulty in introducing enough amount of metal ions or side effects of the metal ions.
To overcome the said disadvantage, patent reference 2 proposed a room temperature processing method of ceramic scaffold. According to this method, a ceramic scaffold can be prepared at room temperature, so that it can include a drug or a growth factor which is vulnerable to heat. Polyphenol, a natural substance which has long been used to prevent osteoporosis, has the effect of promoting the osteoblast activity and the effect of inhibiting the osteoclast activity. However, these effects are expected when it is administered for a long term via oral-administration and there is no case report so far to use this material as an additive to a scaffold or to a bone graft material to increase the local bone regeneration. If it is possible to introduce a natural substance that is effective in controlling osteoblasts and/or osteoclasts into a scaffold even so as to make long time sustained-release of this material possible, it could lead a way to successful preparation of a novel porous scaffold applicable to osteoporosis patient without worry about side effects caused by the conventional bisphosphonate, estrogen, and calcitonin, high costs for growth factor, and difficult process.
Thus, the present inventors continued study on the scaffold for hard tissue regeneration that is applicable to osteoporosis patient. And as a result, the inventors established a method to introduce a polyphenol-based natural substance to a ceramic scaffold evenly, which is represented by Quercetein or Genistein that has less side effects than the conventional osteoporosis treating agent bisphosphonate and can promote the osteoblast activity but inhibit the osteoclast activity so as to increase bone regeneration effect, and further prepared a scaffold for hard tissue regeneration that is suitable for sustained-release of the active ingredient for bone formation, leading to the completion of this invention.